What medications can cause hypokalemia?

Medications That Cause Hypokalemia

The most common medications causing hypokalemia are loop diuretics (furosemide), thiazide diuretics (hydrochlorothiazide, chlorthalidone), corticosteroids, ACTH, high-dose penicillin antibiotics, laxatives (with prolonged use), and hydralazine through RAAS activation. 1, 2, 3

Primary Offenders: Diuretics

Loop Diuretics

• Furosemide causes hypokalemia by reducing sodium reabsorption via the NKCC transporter in the loop of Henle, leading to increased potassium excretion to maintain electrical neutrality 4
• Risk is particularly high with brisk diuresis, inadequate oral electrolyte intake, cirrhosis, or restricted salt intake 2
• Serum potassium should be monitored frequently during the first few months of therapy and periodically thereafter 2

Thiazide Diuretics

• Hydrochlorothiazide and chlorthalidone inhibit the sodium-chloride transporter in the distal tubule, causing increased sodium delivery to the cortical collecting duct with consequent increased potassium excretion via ROMK2 channels 4
• Chlorthalidone carries a 3-fold higher risk of hypokalemia compared to hydrochlorothiazide (adjusted hazard ratio 3.06) due to its longer half-life and greater potassium-depleting effect 1
• The diuretic-induced natriuresis causes upregulation of aldosterone-sensitive ENaC channels, further enhancing potassium loss 4
• Clinically significant hypokalemia is consistently less common with 12.5 mg hydrochlorothiazide than higher doses 3
• Prevalence ranges from 7-56% in patients taking thiazide diuretics 5

Secondary Medication Causes

Hormonal Agents

• Corticosteroids and ACTH intensify electrolyte depletion, particularly hypokalemia, when used concomitantly with diuretics 2, 3
• These agents should be monitored closely as they compound potassium losses 4

Antibiotics

• Penicillin G and other penicillin derivatives can cause potassium wasting 1

Cardiovascular Medications

• Hydralazine stimulates the renin-angiotensin-aldosterone system, leading to increased potassium excretion 1

Other Agents

• Prolonged laxative use contributes to hypokalemia through gastrointestinal potassium losses 2
• Licorice in large amounts causes potassium depletion 2
• Sodium bicarbonate can cause hypokalemia and requires close monitoring with potential potassium supplementation 1

High-Risk Populations

• Women and Black patients have higher risk of thiazide-induced hypokalemia 5
• Elderly patients are at increased risk, particularly with higher diuretic doses 6
• Patients with edematous states require closer monitoring 6
• Patients on digitalis therapy face exaggerated metabolic effects of hypokalemia, especially myocardial effects and arrhythmias 2, 7

Dose-Dependent Relationships

• Higher diuretic doses cause more severe hypokalemia in a dose-dependent manner 1
• Reducing hydrochlorothiazide from 25 mg to 12.5 mg preserves most blood pressure-lowering effect while significantly reducing adverse effects including hypokalemia 8
• In one study, serum potassium decreased progressively from 4.5 mEq/L at baseline to 2.4 mEq/L on 200 mg daily hydrochlorothiazide 7

Critical Drug Interactions

• Triple combination of ACE inhibitor + ARB + MRA is NOT recommended due to excessive hyperkalemia risk, but dual therapy increases hypokalemia risk when MRA is omitted 4
• NSAIDs may attenuate diuretic effects and should be avoided unless essential 4, 3
• The occurrence of premature ventricular contractions correlates significantly with the fall in serum potassium (r = 0.72, p < 0.001), particularly during exercise 7

Monitoring Requirements

• Check serum potassium, creatinine, and electrolytes every 5-7 days after treatment initiation until stable, then every 3-6 months 1
• Monitor within 4 weeks of initiation or dose escalation for hydrochlorothiazide 8
• More frequent monitoring is needed when initiating therapy, changing doses, or in patients with cirrhosis, vomiting, or receiving parenteral fluids 2, 3